Network meta-analysis

Percent body weight change

Overweight or obesity without diabetes (adults)

weeks 40 to 104 (target week 68)Treatment policyDoses of a drug pooledMean difference

Randomized trials

Treatments

3,838

Participants

Trial arms

In plain language

Across 5 trials with 3,838 participants, 3 of 3 treatments had a clearly better result than placebo on percent body weight change. The most favorable estimate was for Tirzepatide injection: mean difference -20.65 percentage points (95% credible interval -25.21 to -15.09).

Lower values favor the treatment. "Clearly" means the 95% credible interval excludes no difference. These are averages across trials; they do not say how any one person will respond. Not medical advice.

Network of trials

Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.

Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Effects compared with Placebo

Mean difference in percentage points. Lower values favor the treatment.

Versus Placebo. Blue: Bayesian random effects posterior median with 95% credible interval (thick) and 95% prediction interval (dashed). Amber diamond: frequentist estimate with 95% confidence interval. Hover over or tab to a row for its values.

Effects of each treatment versus Placebo
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Tirzepatide injection TIRZ_SC	-20.65 (-25.21 to -15.09)	-26.87 to -13.30	-20.90 (-23.96 to -17.84)	Better
Semaglutide injection SEMA_SC	-12.08 (-14.53 to -9.15)	-17.36 to -6.28	-12.08 (-13.43 to -10.73)	Better
Survodutide injection SURV_SC	-8.79 (-13.56 to -3.44)	-15.09 to -1.34	-8.90 (-11.92 to -5.88)	Better

Ranking

How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.

League table

Every treatment against every other: mean difference of the row treatment versus the column treatment, posterior median and 95% credible interval. Green: row clearly better; red: row clearly worse.

Every treatment in a row compared with every treatment in a column
Row versus column	PLACEBO	TIRZ_SC	SEMA_SC	SURV_SC
PLACEBO	PLACEBO	20.65 15.09 to 25.21	12.08 9.15 to 14.53	8.79 3.44 to 13.56
TIRZ_SC	-20.65 -25.21 to -15.09	TIRZ_SC	-8.59 -14.14 to -2.75	-11.90 -18.79 to -4.59
SEMA_SC	-12.08 -14.53 to -9.15	8.59 2.75 to 14.14	SEMA_SC	-3.29 -8.95 to 2.32
SURV_SC	-8.79 -13.56 to -3.44	11.90 4.59 to 18.79	3.29 -2.32 to 8.95	SURV_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 1.431 (95% CrI 0.200 to 5.177)
Residual deviance: 10.1 for 10 data points
DIC: 19.8 (pD 9.7)
Largest R-hat: 1.001
Smallest ESS: bulk 2,098, tail 3,111
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 35^2); PR03 N(0, 17.5^2); PR07 half normal(0, 3.5^2) on tau

Frequentist check (netmeta)

Method: inverse variance, REML, MD
Tau: 0.974
I squared: 69%
Q (total): 6.50 on 2 df, P = 0.039
Q (between designs): 0.00

Inconsistency

Do trials comparing two treatments directly agree with the indirect evidence through other treatments?

No comparison here has both direct and indirect evidence, so inconsistency cannot be checked by node splitting; the between designs Q above is the global check.

Small study effects

A comparison adjusted funnel plot: each point is one trial comparison, centered on its own network estimate. Asymmetry can signal that small trials with unfavorable results are missing.

Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.

Baseline characteristics of the trials

The baseline value of each effect modifier or prognostic factor that applies here, per trial: mean or percent over arms, weighted by the number randomized. A note under a value names a stand in (a median for a mean, 100 minus the male share, Asian subgroup rows, an all Asian site list); "not reported" means no source of the trial prints it.

Baseline effect modifiers and prognostic factors per trial
Trial	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 4 of 5	Type 2 diabetes share in weight trials (percent of participants) effect modifier; 5 of 5	Sex (percent female) effect modifier, prognostic factor; 5 of 5	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 5 of 5	Treatment duration (weeks) effect modifier; 5 of 5	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 5 of 5
STEP 1 S000144	37.87	0 population codes	74.07	13.33	68	standard
STEP 5 S000214	38.55	0 population codes	77.6	0.65	104	standard
STEP 3 S000988	38	0 population codes	81.01	1.8	68	intensive
SURMOUNT-3 S002157	35.9	0 population codes	62.9	0.7	72	standard
NCT04667377 S002375	body weight 105.7 kg	0 population codes	67.7	10.34	46	standard

Comparability of the trials

Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.

FlagBaseline, Treatment duration: design means range from 46.0 (PLACEBO vs SURV_SC) to 80.0 (PLACEBO vs SEMA_SC) weeks; threshold 26
FlagOutcome assessment, definition: confounded with design: not stated 3, percent change in body weight from baseline, planned maintenance dose 1, percent change in body weight from randomization 1
NoteOutcome assessment, time point: selected time points span 46 to 72 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 4, modified_itt 1
NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 2, treatment_policy 3
NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 4, treatment_policy 1
NoteData handling, input conversions: arms_combined 1

Comparability items per trial
Trial	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
STEP 1	68	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2018	adults; BMI 30 or more, or 27 or more with a weight related condition; no diabetes; HbA1c below 6.5 percent
STEP 5	52	full_analysis	not stated	not stated	not stated	not stated	treatment_policy	treatment_policy	double_blind	industry	2018	age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent
STEP 3	68	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2018	BMI 30 or more, or 27 with comorbidity; no type 2 diabetes
SURMOUNT-3	72	modified_itt	percent change in body weight from randomization	not stated	not stated	not stated	treatment_policy	not stated	double_blind	industry	2021	age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; at least 5 percent loss in lead in
NCT04667377	46	full_analysis	percent change in body weight from baseline, planned maintenance dose	not stated	not stated	not stated	treatment_policy	not stated	double_blind	industry	2021	age 18 to under 75; BMI 27 or more; HbA1c below 6.5 percent; weight 70 kg women or 80 kg men or more

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the mean difference on the analysis scale against the trial's first row. Flags mark converted, combined or approximated inputs.

Trial data entering this analysis
Trial	Arm	Treatment	Week	Data	Value	SE	Events / N	Flags	Source
STEP 1	A1	SEMA_SC	68	arm, percent_change	-15.600	0.279	1,306		registry:outcomes
STEP 1	A2	PLACEBO	68	arm, percent_change	-2.800	0.254	655		registry:outcomes
STEP 5	A1	SEMA_SC	52	arm, percent_change	-15.600	0.700	152		R0021896:Table 2
STEP 5	A2	PLACEBO	52	arm, percent_change	-3.000	0.700	152		R0021896:Table 2
STEP 3	A1	SEMA_SC	68	arm, percent_change	-16.500	0.501	407		registry:outcomes
STEP 3	A2	PLACEBO	68	arm, percent_change	-5.800	0.539	204		registry:outcomes
SURMOUNT-3	A1	TIRZ_SC	72	arm, percent_change	-18.400	0.700	287		R0007405:Table 4
SURMOUNT-3	A2	PLACEBO	72	arm, percent_change	2.500	1.000	292		R0007405:Table 4
NCT04667377	A1+A2+A3+A4	SURV_SC	46	arm, percent_change	-11.720	0.547	306	arms_combined	registry:outcomes
NCT04667377	A5	PLACEBO	46	arm, percent_change	-2.820	1.060	77		registry:outcomes

Rerun this analysis yourself

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